1653P - Dicer and Drosha Expression and Response to Bevacizumab-Based Therapy in Advanced Colorectal Cancer Patients

Abstract

ABSTRACT Introduction The miRNA-regulating enzyme Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced CRC patients. Methods We measured Dicer and Drosha messenger RNA (mRNA) levels in formalin-fixed paraffin-embedded specimens of advanced CRC treated with (n = 76) or without (n = 28) Bevacizumab-containing regimens and patients with diverticulosis (normal mucosa) (n = 20), using a quantitative reverse-transcriptase-polymerase-chain reaction assay, and compared the results with clinical outcome. Results We found that lower Dicer levels predicted a longer Progression-Free Survival (PFS) (P = .0001) and Overall Survival (OS) (P = .031) in Bevacizumab-treated patients. Conversely, Drosha levels were not associated with prognosis. Low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (2.6% complete responses and 43.4% partial responses versus 1.3% and 28.9%, respectively; P = .045). Multivariate analysis identified three independent predictors of improved OS: high performance status [Relative Risk (RR) 1.56; P = .009], lower organs involvement (RR 0.72; P = .025) and low Dicer expression (RR 0.62; P = .009). Importantly, Dicer and Drosha expression did not correlate with outcome in not Bevacizumab-treated patients. Moreover we analysed Dicer and Drosha mRNA levels; our results showed a significantly higher Drosha expression in primary tumors than in normal mucosa (P = Conclusions These findings suggest that decreased Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRC treated with Bevacizumab-based therapy. Disclosure All authors have declared no conflicts of interest.